Pyrrole-Linked Benzimidazolyl Hydrazone Self-Assembly Forms HCl Channels and Induces Apoptosis in Cancer Cells.

Modulation of intracellular chloride ion concentration by artificially developed ion transporters has been known to induce apoptosis in cancer cells. However, most of these transporters cause harm to healthy cells as well, limiting their applicability in real biological systems. Here, we report a pyrrole-linked benzimidazolyl-hydrazone that self-assembles to form a nanochannel assembly across the lipid bilayer, enabling the selective translocation of HCl, a system rarely reported in the literature.

Mapping the metabolic perturbations associated with palmitate-induced oxidative stress and development of insulin resistance in skeletal muscle cells.

The development of insulin resistance (IR) in the skeletal muscle has been identified as one of the hallmarks of Type 2 diabetes mellitus (T2DM). Studies have shown that palmitic acid (PA), a saturated free fatty acid (FFA), can contribute to the development of IR in various insulin-responsive tissues via the induction of oxidative stress and mitochondrial dysfunction. The specific molecular mechanisms and metabolic changes that lead to IR development are not completely defined, and a better understanding of these mechanisms is needed.

Visualization of Early and Late Molecular Events Associated with the Development of Type 1 Diabetes Using NMR Spectroscopy.

Type 1 diabetes mellitus (T1DM) is an autoimmune disorder caused by the loss of insulin-producing pancreatic β-cells. This study aims to explore the correlation between hyperglycemia and concurrent metabolic perturbations during T1DM development to help identify biomarkers that differentiate between the early and established stages. Streptozotocin (STZ), a glucosamine nitrosourea compound, induces T1DM.

Metabolic perturbations associated with hIAPP-induced insulin resistance in skeletal muscles: Implications to the development of type 2 diabetes.

The human islet amyloid polypeptide (hIAPP) tends to misfold and self-assemble to form amyloid fibrils, which has been associated with the loss of function and viability of pancreatic β-cells in type 2 diabetes mellitus (T2DM). The role of hIAPP in the development of insulin resistance (a hallmark of T2DM) in skeletal muscles - the major sites for glucose utilization - needs further investigation. Even though, insulin-resistant conditions have been known to stimulate hIAPP aggregation, the events that lead to the development of insulin resistance due to hIAPP aggregation in skeletal muscles remain unidentified.

Correction: Molybdenum-maltolate as a molybdopterin mimic for bioinspired oxidation reaction.

Correction for 'Molybdenum-maltolate as a molybdopterin mimic for bioinspired oxidation reaction' by Swapnil S. Pawar , , 2024, , 5770-5774, https://doi.org/10.

Bisindole-based small molecules as transmembrane anion transporters and potential anticancer agents.

Few synthetic ion transporters have been reported incorporating indole as the core moiety. We have developed a novel bisindole-based transporter capable of efficient transmembrane anion antiport. This system induced cytotoxicity in MCF-7 breast cancer cells chloride ion homeostasis disruption and the associated ROS generation, mitochondrial membrane depolarization, and lysosomal deacidification.

Molybdenum-maltolate as a molybdopterin mimic for bioinspired oxidation reaction.

A novel -dioxomolybdenum(VI)-maltolate [MoO(Mal)] (1) is prepared as a stable molybdopterin model for the biomimetic catalysis of the oxidation of hypoxanthine in acetonitrile-water at room temperature. Compound 1 efficiently catalyzes the oxidation reaction of toluene, diphenylmethane, and styrene. Cyto- and oral-toxicity studies suggest its tremendous potential for application as a molybdenum supplement.

NAD(P)H:Quinone Acceptor Oxidoreductase 1 (NQO1) Activatable Salicylamide H /Cl Transporters.

NAD(P)H:quinone acceptor oxidoreductase 1 (NQO1), a detoxifying enzyme overexpressed in tumors, plays a key role in protecting cancer cells against oxidative stress and thus has been considered an attractive candidate for activating prodrug(s). Herein, we report the first use of NQO1 for the selective activation of 'protransporter' systems in cancer cells leading to the induction of apoptosis. Salicylamides, easily synthesizable small molecules, have been effectively used for efficient H /Cl symport across lipid membranes.

A Benzohydrazide-Based Artificial Ion Channel that Modulates Chloride Ion Concentration in Cancer Cells and Induces Apoptosis by Disruption of Autophagy.

Fluctuations in the intracellular chloride ion concentration, mediated by synthetic ion transporters, have been known to induce cytotoxicity in cells by disrupting ionic homeostasis. However, the activity of these transporters in modulating autophagy remains largely unexplored. Here, we report a benzoylbenzohydrazide () that self-assembles to form a supramolecular nanochannel lumen that allows selective and efficient transport of chloride ions across the cell membranes, disrupts ion homeostasis, and thus leads to the induction of apoptosis in cancer cells.

Human islet amyloid polypeptide: A therapeutic target for the management of type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) and other metabolic disorders are often silent and go unnoticed in patients because of the lack of suitable prognostic and diagnostic markers. The current therapeutic regimens available for managing T2DM do not reverse diabetes; instead, they delay the progression of diabetes. Their efficacy (in principle) may be significantly improved if implemented at earlier stages.

Unravelling the inhibitory activity of Chlamydomonas reinhardtii sulfated polysaccharides against α-Synuclein fibrillation.

α-Synuclein (α-Syn) is an intrinsically disordered presynaptic protein, whose aggregation is critically involved in Parkinson's disease (PD). Many of the currently available drugs for the treatment of PD are not sufficiently effective in preventing progress of the disease and have multiple side-effects. With this background, efficient drug candidates, sulfated polysaccharides from Chlamydomonas reinhardtii (Cr-SPs) were isolated and investigated for their effect on inhibition of α-Syn fibrillation and dissolution of preformed α-Syn fibrillar structures through a combination of spectroscopic and microscopic techniques.

Aqueous extract of Triphala inhibits cancer cell proliferation through perturbation of microtubule assembly dynamics.

Triphala (Trl) is an ayurvedic formulation used for treating disorders of the digestive, respiratory, and nervous systems. Its anticancer properties have also been documented. We studied effects of Trl on tubulin, a target protein for several anticancer drugs, and systematically elucidated a possible antiproliferative mechanism of action of Trl.

Synergistic Inhibition of Protein Fibrillation by Proline and Sorbitol: Biophysical Investigations.

We report here interesting synergistic effects of proline and sorbitol, two well-known chemical chaperones, in the inhibition of fibrillation of two proteins, insulin and lysozyme. A combination of many biophysical techniques has been used to understand the structural morphology and modes of interaction of the chaperones with the proteins during fibrillation. Both the chaperones establish stronger polar interactions in the elongation and saturation stages of fibrillation compared to that in the native stage.